Concurrent pembrolizumab with AVD for untreated classical Hodgkin lymphoma

Abstract

Concurrent administration pembrolizumab with chemotherapy in untreated classical Hodgkin lymphoma (CHL) has not previously been studied. To investigate this combination, we conducted a single arm study of concurrent pembrolizumab with AVD (APVD) for untreated CHL. We enrolled 30 patients (6 early favorable, 6 early unfavorable, and 18 advanced stage, median age 33 years (range 18-69 years)) and met the primary safety endpoint with no observed significant treatment delays in the first two cycles. Twelve patients experienced grade 3-4 non-hematologic adverse events (AEs) most commonly febrile neutropenia (5, 17%) and infection/sepsis (3, 10%). Grade 3-4 immune-related AEs were seen in 3 patients, including ALT elevation (3, 10%) and AST elevation (1, 3%). One patient experienced an episode of grade 2 colitis and arthritis. Six (20%) patients missed at least one dose of pembrolizumab due to adverse events, primarily grade 2 or higher transaminitis (5, 17%). Among 29 response-evaluable patients, the best overall response rate was 100% and CR rate of 90%. With median follow up of 2.1 years, 2-year progression-free survival (PFS) and overall survival were 97% and 100%, respectively. To date, no patient who withheld or discontinued pembrolizumab due to toxicity has progressed. Clearance of ctDNA was associated with superior PFS when measured after cycle 2 (p=0.025) and at end of treatment (EOT, p=0.0016). None of the 4 patients with persistent disease by FDG-PET at EOT yet negative ctDNA have relapsed to date. Concurrent APVD shows promising safety and efficacy, but may yield spurious PET findings in some patients. Trial Registration Number: NCT03331341

The shifting roles and toxicities of cellular therapies in B‐cell malignancies

“…Guidelines are often institution specific and vary across inhibitor may also reduce the number of patients who will require this therapy. 19,20 The use of these frontline agents also impacts the salvage chemotherapy options used to induce remission ahead of ASCT.…”

“…no active cardiopulmonary symptoms or marked organ dysfunction identified on non‐invasive cardiopulmonary testing), and social health/support (no active substance abuse disorder, presence of a caregiver able to support for at least first 2 weeks following hospital discharge from transplant). Recently, improvements in survival and relapse in the front‐line setting with the incorporation of brentuximab to standard chemotherapy (doxorubicin, vinblastine, dacarbazine [AVD]) and with nivolumab‐AVD, a programmed‐death 1 inhibitor may also reduce the number of patients who will require this therapy 19,20 …”

Immune checkpoint inhibitors in advanced and relapsed/refractory Hodgkin lymphoma: current applications and future prospects

“…However, the paradigm of response-adapted therapy, which relies on positron emission tomography (PET) scans for response assessment after cycle 2 (PET2), presents challenges in the context of ICIs. Multiple trials combining ICIs with chemotherapy have indicated that PET2 does not predict treatment response as well as cytotoxic chemotherapy & targeted therapy alone ( 11 ). This discrepancy has been attributed to the higher PET2 positive rate observed in the presence of ICIs, which has not been associated with lower progression-free survival (PFS).…”

“…This discrepancy has been attributed to the higher PET2 positive rate observed in the presence of ICIs, which has not been associated with lower progression-free survival (PFS). As an alternative, circulating tumor DNA (ctDNA) analysis has emerged as a more reliable predictor of response, suggesting the potential for integrating ctDNA into risk stratification models ( 11 ).…”

Patient preferences in the treatment of stage III/IV classic Hodgkin lymphoma: Results from the CONNECT cross‐sectional survey

“…9 In ECHELON-1, patients treated with A + AVD compared with ABVD had a 41% reduction in the risk of death (HR: 0.59; 95% CI: 0.40-0.88; p = 0.009). As of late 2023, studies are evaluating other front-line treatments in patients with advanced-stage cHL [10][11][12][13][14] ; however, results from these studies are immature and available only as conference proceedings.…”